The mammalian auditory organ, the organ of Corti (OC), is composed of mechanosensory hair cells and nonsensory supporting cell types. Based on their morphology and physiology, at least two types of ... [more ▼]

The mammalian auditory organ, the organ of Corti (OC), is composed of mechanosensory hair cells and nonsensory supporting cell types. Based on their morphology and physiology, at least two types of sensory cells can be identified in the OC: inner and outer hair cells. The structure of this organ is well reported in adult but its development is still little-known. By using confocal microscopy, we studied the spatial-temporal distribution of beta tubulin III during the differentiation of the OC in rat from the embryonic day 18 (E18) to the postnatal day (P25). The beta tubulin III is typical for neural cells in the OC. We observed that beta III tubulin is present in the extensions innerving the row of inner hair cells at E18. At E19, the extensions innerving the inner hair cells and the two first rows of outer hair cells were immunolabelled. From E21 to P25, all of hair cells were connected to the spiral ganglion. In the latter, the intensity of immunolabelling decreased between E18 to P25 and the labelling only concerned some cells. These results reveal that beta III tubulin appears before birth in the nervous extensions connecting the sensory cells of the OC according to a modiolar-to-striolar gradient. In the spiral ganglia, the labelling progressively decreases during its development. [less ▲]

Mitochondrial F(1)F(O) ATP synthase (Complex V) catalyses ATP synthesis from ADP and inorganic phosphate using the proton-motive force generated by the substrate-driven electron transfer chain. In this work, we investigated the impact of the loss of activity of the mitochondrial enzyme in a photosynthetic organism. In this purpose, we inactivated by RNA interference the expression of the ATP2 gene, coding for the catalytic subunit beta, in the green alga Chlamydomonas reinhardtii. We demonstrate that in the absence of beta subunit, complex V is not assembled, respiratory rate is decreased by half and ATP synthesis coupled to the respiratory activity is fully impaired. Lack of ATP synthase also affects the morphology of mitochondria which are deprived of cristae. We also show that mutants are obligate phototrophs and that rearrangements of the photosynthetic apparatus occur in the chloroplast as a response to ATP synthase deficiency in mitochondria. Altogether, our results contribute to the understanding of the yet poorly studied bioenergetic interactions between organelles in photosynthetic organisms. [less ▲]

in Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society (2010), 58(7), 635-51

Ascorbate and menadione (Apatone) in a ratio of 100:1 kills tumor cells by autoschizis. In this study, vitamin-induced changes in nucleolar structure were evaluated as markers of autoschizis. Human ... [more ▼]

Ascorbate and menadione (Apatone) in a ratio of 100:1 kills tumor cells by autoschizis. In this study, vitamin-induced changes in nucleolar structure were evaluated as markers of autoschizis. Human bladder carcinoma (T24) cells were overlain with vitamins or with culture medium. Supernatants were removed at 1-hr intervals from 1 to 4 hr, and the cells were washed with PBS and prepared for assay. Apatone produced marked alterations in nucleolar structure including redistribution of nucleolar components, formation of ring-shaped nucleoli, condensation and increase of the proportion of perinucleolar chromatin, and the enlargement of nucleolar fibrillar centers. Immunogold labeling of the nucleolar rRNA revealed a granular localization in treated and sham-treated cells, and immunogold labeling of the rDNA revealed a shift from the fibrillar centers to the condensed perinucleolar chromatin. Fibrillarin staining shifted from the fibrillar centers and adjacent regions to a more homogeneous staining of the entire nucleolus and was consistent with the percentage of autoschizic cells detected by flow cytometry. Because autoschizis entails sequential reactivation of DNase I and DNase II, and because the fibrillarin redistribution following DNase I and Apatone treatment is identical, it appears that the nucleolar and fibrillarin changes are markers of autoschizis. [less ▲]

The nucleolus is the ribosome factory of the cells. This is the nuclear domain where ribosomal RNAs are synthesized, processed, and assembled with ribosomal proteins. Here we describe the classical ... [more ▼]

The nucleolus is the ribosome factory of the cells. This is the nuclear domain where ribosomal RNAs are synthesized, processed, and assembled with ribosomal proteins. Here we describe the classical tripartite organization of the nucleolus in mammals, reflecting ribosomal gene transcription and pre-ribosomal RNA (pre-rRNA) processing efficiency: fibrillar center, dense fibrillar component, and granular component. We review the nucleolar organization across evolution from the bipartite organization in yeast to the tripartite organization in humans. We discuss the basic principles of nucleolar assembly and nucleolar structure/function relationship in RNA metabolism. The control of nucleolar assembly is presented as well as the role of pre-existing machineries and pre-rRNAs inherited from the previous cell cycle. In addition, nucleoli carry many essential extra ribosomal functions and are closely linked to cellular homeostasis and human health. The last part of this review presents recent advances in nucleolar dysfunctions in human pathology such as cancer and virus infections that modify the nucleolar organization. [less ▲]

The cochleo-vestibular ganglion contains neural crest-derived glial cells and sensory neurons that are derived from the neurogenic otic placode. Little is known about the molecular mechanisms that ... [more ▼]

The cochleo-vestibular ganglion contains neural crest-derived glial cells and sensory neurons that are derived from the neurogenic otic placode. Little is known about the molecular mechanisms that regulate the tightly orchestrated development of this structure. Here, we report that Sox10, a high-mobility group DNA-binding domain transcription factor that is required for the proper development of neural crest cell derivatives, is specifically expressed in post-migratory neural crest cells in the cochleo-vestibular ganglion. Using Sox10-deficient mice, we demonstrate that this transcription factor is essential for the survival, but not the generation, of the post-migratory neural crest cells within the inner ear. In the absence of these neural crest-derived cells, we have investigated the survival of the otocyst-derived auditory neurons. Surprisingly, auditory neuron differentiation, sensory target innervation and survival are conserved despite the absence of glial cells. Moreover, brain-derived neurotrophic factor expression is increased in the hair cells of Sox10-deficient mice, a compensatory mechanism that may prevent spiral ganglion neuronal cell death. Taken together, these data suggest that in the absence of neural crest-derived glial cells, an increase trophic support from hair cells promotes the survival of spiral ganglion neurons in Sox10 mutant mice. [less ▲]

The mammalian auditory organ, the organ of Corti (OC), is composed of mechanosensory hair cells and nonsensory supporting cell types. Based on their morphology and physiology, a least four types of ... [more ▼]

The mammalian auditory organ, the organ of Corti (OC), is composed of mechanosensory hair cells and nonsensory supporting cell types. Based on their morphology and physiology, a least four types of supporting cells can be identified in the OC: inner pillar cell, outer pillar cell, phalangeal cell and Deiter’s cells. The structure of this organ is well reported in adult but its development is still little known. Using antibodies directed against different proteins of intermediate filaments cytoskeleton, we studied the spatial-temporal localization of cytokeratins (typical of epithelial cells) and vimentin (typical of mesenchymal cells) during the differentiation of the OC in rat from the embryonic day 18 (E18) to the postnatal day (P15). Whatever the antibody used, we observed an obvious labelling over the supporting cells after the birth. In particular, an intense labelling is observed in the pillar cells and in the Deiters’ cells at P8 and at P10. These results suggest that the epithelial-mesenchymal transition might be implicated in the opening of Corti’s tunnel between the pillar cells and the formation of the Nuel’s spaces between the Deiters’ cell and their outer hair cells, at P8 and at P10 respectively. [less ▲]

The mammalian auditory organ, the organ of Corti (OC), is composed of mechanosensory hair cells and nonsensory supporting cell types. Based on their morphology and physiology, a least four types of ... [more ▼]

The mammalian auditory organ, the organ of Corti (OC), is composed of mechanosensory hair cells and nonsensory supporting cell types. Based on their morphology and physiology, a least four types of supporting cells can be identified in the OC: inner pillar cell, outer pillar cell, phalangeal cell and Deiter’s cells. All supporting cells are highly specialized cells that are characterized by the presence of bundled microtubules with 15 protofilaments instead of 13. Using antibobies against different proteins of cytoskeleton (tubulin, cutokeratin and vimentin), we investigated by confocal microscopy the setting up of supporting cells' cytoskeleton during the differentiation of the OC in art from the embryonic day 18 (E18) to the postnatal 15 (P15). We showed that the inner pillar cells are labelled with an anti-beta IV tubulin from P0. Using an antibody to cytokeratin, a labelling appeared in Deiters' cells from E22. We also revealed that during the development of the OC, supporting cells were labelled with an anti-vimentin antibody from P0. [less ▲]

The present study aims at investigating the mechanism by which MT4-MMP, a membrane-anchored MMP expressed by human breast tumor cells promotes the metastatic dissemination into lung. We applied ... [more ▼]

The present study aims at investigating the mechanism by which MT4-MMP, a membrane-anchored MMP expressed by human breast tumor cells promotes the metastatic dissemination into lung. We applied experimental (intravenous) and spontaneous (subcutaneous) models of lung metastasis using human breast adenocarcinoma MDA-MB-231 cells overexpressing or not MT4-MMP. We found that MT4-MMP does not affect lymph node colonization nor extravasation of cells from the bloodstream, but increases the intravasation step leading to metastasis. Ultrastructural and fluorescent microscopic observations coupled with automatic computer-assisted quantifications revealed that MT4-MMP expression induces blood vessel enlargement and promotes the detachment of mural cells from the vascular tree, thus causing an increased tumor vascular leak. On this basis, we propose that MT4-MMP promotes lung metastasis by disturbing the tumor vessel integrity and thereby facilitating tumor cell intravasation. [less ▲]